PROJECT 3: CONSEQUENCES OF FOCAL BRAIN LESIONS ACQUIRED DURING DEVELOPMENT Lesion method studies of individuals who have sustained childhood-onset focal brain damage are an important means of gathering more precise descriptions of brain-behavior relationships in developmental disorders. Conditions causing focal brain damage in childhood are not common, but we have developed effective mechanisms of enrolling a sufficient number of patients for systemic studies. During the current funding period we have established a registry of patients with early-onset focal brain damage, and have collected comprehensive neuropsychological data characterizing their cognition, emotion, and psychosocial functioning. Here we propose to conduct a series of hypothesis-driven studies designed to further delineate the neuropsychological and neuroanatomical factors that contribute to the chronic impairments of cognition, emotion, and social behavior that characterize some patients with childhood-onset brain damage. We will continue the longitudinal study of the patients in the registry, as well as newly enrolled patients, using: (1) precise description of brain lesions using MRI and 3-D reconstruction, (2) comprehensive characterization of cognition and behavior with standardized, age-appropriate neuropsychological measures, (3) standardized indices of functional outcome (academic achievement, employment, social adjustment), (4) experimental measures of cognition and behavior, with a focus on emotion and social competence, and (5) analysis of gray and white matter structure in brain regions functionally associated with the damaged area. Delineation of relationships between damage to specific neural systems early in life and the short- and long-term consequences for cognition, emotion, and behavior is providing fundamental information of relevance to the understanding of human development and of importance for better evaluation and treatment of neurobehavioral disorders with onset in childhood. Public health relevance: Developmental disorders of cognition, emotion, and social behavior present a major public health burden, but their underlying brain mechanisms remain poorly understood. This research provides a unique and important source of information regarding the neural bases of cognition, emotion, and their interaction during development.